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Biomedical subjects

J C Davis

Publications and source records attributed to J C Davis.

At least 55 records · Page 3Linked to original sources
PubMed1998

A pilot study of 2-chloro-2'-deoxyadenosine in the treatment of systemic lupus erythematosus-associated glomerulonephritis.

OBJECTIVE: To determine the safety and tolerability, as well as the clinical and immunologic effects, of 2-chloro-2'-deoxyadenosine (2-CdA) in patients with systemic lupus erythematosus-associated glomerulonephritis. METHODS: In a phase I study, 12 patients with proliferative lupus nephritis received 2-CdA either in weekly escalating intravenous treatments (0.15 mg/kg/week x 4, 0.1875 mg/kg/week x 4, 0.225 mg/kg/week x 4; n = 5) or in a continuous 7-day infusion (0.05 mg/kg/day; n = 7). Safety, renal improvement, and immunologic effects were evaluated for 12 months. RESULTS: Patients treated with 2-CdA showed peripheral lymphocyte depletion without a significant reduction in neutrophil, monocyte, or platelet numbers or hematocrit levels. Naive and memory T cells were decreased, as were lymphocytes with markers of early and late activation. Peripheral B cell depletion was not associated with significant decreases in serum immunoglobulin levels. Continuous infusion induced better clinical responses than weekly infusions, as evidenced by 1) the percentage of patients showing complete response (43% versus 0%), 2) the percentage with at least 50% reduction in proteinuria (43% versus 20%), 3) the percentage with at least a 50% reduction in urinary dysmorphic red cells (57% versus 0%), and 4) the percentage in whom cellular casts disappeared (43% versus 0%). Several infections occurred; these responded to standard antibiotic therapy. CONCLUSION: In this pilot study, 2-CdA was safely administered to 12 patients with lupus nephritis. It induced prolonged reductions in lymphocyte populations and may be efficacious in selected patients with lupus nephritis when administered as a continuous infusion.

Adult↗
PubMed1998

Angiotensin I converting enzyme gene polymorphisms in systemic lupus erythematosus: decreased prevalence of DD genotype in African American patients.

The presence of the D (deletion) allele at the angiotensin converting enzyme (ACE) gene has been associated with a) adverse vascular events contributing to early mortality and b) progressive deterioration of renal function in a variety of chronic glomerular diseases. We investigated the potential role of ACE polymorphisms in patients with systemic lupus erythematosus (SLE). Two hundred and sixteen (216) SLE patients (121 Caucasians; 78 African Americans; and 17 other) and 200 normal controls were studied; 134 patients had evidence of renal disease. ACE genotypes were determined by a polymerase chain reaction based assay. The frequency of genotype DD was increased in African American normal controls compared to Caucasians (55% vs. 37%, p = 0.017) and in African American normal controls vs. African American lupus patients (55% vs. 30%, p = 0.008). Trend analysis of the genotype distribution across the three African American groups (renal, non-renal, controls) revealed a trend of increased frequency of I and decreased frequency of D as likelihood of renal disease increases (p = 0.008). No association between any ACE genotype with parameters of renal disease and/or response to therapy was identified. African American patients with lupus have a lower frequency of DD genotype as compared to African American normal controls. Further studies will be necessary to address whether this is due to decreased survival of these patients, a protective effect of DD genotype from developing the disease or a chance sample effect.

Adult↗
PubMed1998

High dose versus low dose fludarabine in the treatment of patients with severe refractory rheumatoid arthritis.

OBJECTIVE: Fludarabine, a nucleoside analog that targets both resting and proliferating lymphocytes, is a promising drug for the treatment of autoimmune diseases. We conducted a 2 dose, open label clinical trial to evaluate the toxicity/safety of the fludarabine treatment and its clinical and immunological effects. METHODS: Twenty-six patients with severe rheumatoid arthritis (RA) refractory to treatment with at least one slow acting antirheumatic drug were treated with intravenous fludarabine [20 mg/m2 body surface area (n=12) or 30 mg/m2 body surface area (n=14) per day for 3 consecutive days] given monthly for 6 months. Second line agents with the exception of glucocorticoids were discontinued at least 4 weeks before study entry. Measurements included toxicity and tolerability monitored at monthly intervals: efficacy, by both a 50% reduction in tender or swollen joint count and American College of Rheumatology (ACR) criteria for 20% response; and phenotypic analysis of peripheral blood mononuclear cells and T cell functional assays. RESULTS: Using intention-to-treat analysis, 2 of 12 (17%) patients in the low dose and 7 of 14 (50%) in the high dose groups had 50% or greater reduction in tender and/or swollen joint count after 6 months of therapy compared to baseline (p=0.09). Two of 12 (17%) in the low dose group and 5 of 14 (36%) in the high dose group met ACR criteria for 20% improvement (p=0.28). No immediate toxicity was observed. Several infections occurred, including 4 episodes of limited Herpes zoster, which responded to standard therapy. Significant lymphopenia involving T and B cells was observed in all patients. Both naive (CD4+CD45RA+) and memory CD4+ T cells (CD4+CD45RO+) were reduced (naive > memory). No significant regeneration of naive T cells was observed, which may suggest limited thymic regenerative capacity. Fludarabine decreased the proliferative response of peripheral blood lymphocytes to mitogens, as well as the production of T cell (interleukin 2 and interferon-gamma) and monocyte derived (tumor necrosis factor-alpha and IL-10) cytokines. CONCLUSION: Fludarabine treatment of patients with severe, refractory RA resulted in significant lymphopenia, suppression of lymphocyte function, and clinical improvement in the high dose group. There was no immediate toxicity; however, several infections occurred. Controlled trials are needed to substantiate the clinical improvement observed in this open label trial.

Antigens, CD↗
PubMed1997

An outbreak of vancomycin-resistant Enterococcus faecium in liver transplant recipients.

Vancomycin-resistant Enterococcus faecium (VREF) has become a significant nosocomial pathogen for immunosuppressed patients. During a 5-month period in 1993, 8 cases of invasive infection with VREF (7 with bacteremia) were identified in liver transplant recipients, half of whom were adults. Epidemiology and microbiology studies were designed to identify the source and to determine the risk factors for this infection. Overall mortality was 50% (3 adults and 1 child). Mortality in bacteremic patients was 57%. A case-control study showed that cases were more likely to have been treated with a third-generation cephalosporin or vancomycin and to have undergone more than four biliary tract procedures. Environmental surveillance cultures yielded only one VREF isolate from a rectal temperature probe, but this device was used in only 2 of the cases. Cultures from all surgery and radiology suites were negative. All VREF isolates were genotyped by contour-clamped homogenous electric field electrophoresis of chromosomal DNA restriction fragments. These studies showed that a single clone was responsible for the outbreak, although other clones could be detected in the hospital. After implementing strict contact isolation on the liver transplant unit, only 1 additional patient with VREF was identified during this outbreak. In conclusion, it was found that antibiotic use and biliary tract manipulation were risk factors for developing invasive infections with VREF after liver transplantation. Optimal treatment is still unclear but most likely includes a combination of two or more antibiotics. Prompt institution of infection control measures can preclude rapid spread of this nosocomial pathogen.

Adolescent↗
PubMed1996

Colonization and infection associated with Malassezia and Candida species in a neonatal unit.

The objectives of this study were to determine, in neonates of < 1250 g birthweight (N = 57), the initial time of skin colonization by Malassezia furfur, rate of colonization by Candida spp., and whether skin colonization by these yeasts was predictive of central line colonization or fungaemia. By age two weeks, 51% of neonates were culture-positive for M. furfur on umbilical or groin skin. During hospitalization, positive skin cultures for M. furfur or Candida spp. were obtained in 70% and 37% of neonates, respectively. Risk factors associated with positive skin cultures were mechanical ventilation and three or more episodes of suspected sepsis. Eight of the 52 infants with central venous catheters, had positive blood cultures withdrawn from the lines; five (62%) of these had positive skin surveillance cultures. Although positive skin cultures for M. furfur, Candida spp., or both were commonly observed in this population, they were not predictive of positive central line cultures or systemic illness.

Candida↗
PubMed1996

Lupus nephritis.

Both immune and nonimmune mechanisms are operant in lupus nephritis. Recent findings have begun to elucidate fundamental questions in the pathogenesis of the disease. Genetic linkage studies have identified susceptibility loci contributing to nephritis in lupus-prone mice. Polymorphisms of the Fc gamma Rlla gene have been found to correlate with the development of renal disease in black Americans and white Europeans. Genetic factors are important in determining both predisposition to nephritis and outcome (and likely response to therapy). In lupus nephritis, prevention of tissue injury involves effective immunosuppressive therapy and aggressive management of hypertension and hyperlipidemia. Although with intensive immunosuppressive therapy most lupus patients achieve remission, a substantial number of these patients either do not respond, respond partially, or relapse after discontinuation of therapy. Moreover, the toxicity of available immunosuppressive drugs is substantial, suggesting that alternative therapeutic regimens are needed. In the future, other inhibitors of inflammatory, immune, vasoactive, proteolytic, and growth-promoting mediators are likely to play a role in the management of lupus nephritis.

Animals↗
PubMed1994

Airborne fungal spore monitoring in a protective environment during hospital construction, and correlation with an outbreak of invasive aspergillosis.

OBJECTIVE: Evaluate aerobiological monitoring for fungal spores during hospital construction and correlate results with an outbreak of invasive aspergillosis (IA). DESIGN: Prospective air sampling for molds was done using the gravity air-settling plate (GASP) method. SETTING: A university medical center special care unit consisting of single-patient rooms with high-efficiency particulate air filtration under positive pressure. PATIENTS: Five neutropenic patients who subsequently developed IA. RESULTS: Four of the five patients with IA were housed in rooms adjacent to a construction staging area. Aerobiological monitoring detected an increase in the number of airborne fungal spores including Aspergillus species in these rooms; however, increased counts preceded IA diagnosis by 1 to 7 days in only three of the five patients. Swab cultures of the exhaust vents within each room confirmed results from air-settling plates. Follow-up monitoring, using the GASP method, demonstrated that control procedures were effective in reducing air mold contamination. CONCLUSION: The GASP method, although able to demonstrate that infection control measures reduced mold contamination of the air, was insensitive to detect levels of mold contaminates in time to prevent IA.

Air Microbiology↗
PubMed1993

Measurement of serum levels of exogenously administered FSH and LH during ovulation induction therapy.

We conducted a prospective study of blood levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) following daily intramuscular injection of human menopausal gonadotropin (hMG) containing equal proportions of FSH and LH. Blood samples were collected on alternate days and the resulting changes in the blood levels of the ovarian hormone estradiol were also monitored. Twenty-eight consecutive patients with polycystic ovary syndrome who were between the ages of 25 and 35 years and attending our infertility clinic for ovulation induction therapy and assisted pregnancy were studied. Polycystic ovary syndrome was diagnosed on laparoscopy and as evidenced by high serum LH which was three times greater than FSH in the follicular phase of the menstrual cycle. A male factor for infertility was excluded. Twenty-five out of 28 women (89.3%) receiving hMG responded to therapy by a rise in serum estradiol level (> 1200 pmol/l on day 9). Of the 25 women who responded to hMG, four had live single babies (16%). All four women showed a cumulative rise in mean serum FSH with treatment when measured by standard radioimmunoassay, reaching statistical significance on day 5 (p < 0.05). The remaining 21 who failed to become pregnant showed variable changes in mean serum FSH with a sharp rise on day 3 (p < 0.02) and a significant fall on day 7 (p < 0.02). However, mean serum LH measured by standard radioimmunoassay in all women remained unchanged throughout the period of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Adjuvant hyperbaric oxygen in malignant external otitis.

Necrotizing invasive pseudomonal infection of the external auditory canal (malignant external otitis) is an uncommon but important disorder in the elderly. The high morbidity, and even mortality, of this disorder has been reduced by the early and intensive use of combination antipseudomonal antibiotics. However, in severely immunocompromised patients or in infection involving the base of the skull, multiple cranial nerves, or the meninges, conventional therapy has been prolonged, intensive, and relatively ineffective. We treated 16 patients with malignant external otitis with adjuvant hyperbaric oxygen therapy. In six patients, infection was in advanced stages, infections were recurrences after previous treatment, and repeated treatment with antipseudomonal antibiotics had failed. All 16 cases responded promptly when a 30-day course of hyperbaric oxygen was added to the antibiotic regimen, and all patients remained free of infection or neurologic deficit during 1 to 4 years of follow-up. No complications of this treatment modality were noted. Hyperbaric oxygen therapy reverses tissue hypoxia, which enhances phagocytic killing of aerobic microorganisms, and stimulates neomicroangiogenesis. In addition, hyperbaric oxygen augments the action of aminoglycoside antibiotics. Adjuvant hyperbaric oxygen therapy should be considered in advanced or recurrent cases of malignant external otitis.

Aged↗
PubMed1992

Psychobiologic responses to exercise at different times of day.

The primary purpose of this investigation was to determine whether selected psychobiologic responses to running exercise vary as a function of the time of day at which exercise is performed. Twelve adult males completed four bouts of randomly assigned, submaximal exercise (20-min runs at 70% VO2max) at 0800, 1200, 1600 and 2000 h. Since selected personality traits have previously been shown to influence circadian rhythms, personality assessments (i.e., Eysenck Personality Questionnaire, EPQ; Morningness-Eveningness Questionnaire, MEQ; Spielberger's State-Trait Anger Expression Inventory, STAIX; and State-Trait Anxiety Inventory, STAI) were made during the initial testing session. The group studied scored within the normal range on the traits assessed by the EPQ, STAIX, and STAI. Also, subjects were not able to be classified as either "morning" or "evening" types based on MEQ scores. Ten minutes before as well as 10 and 20 min following the exercise bouts, state anxiety, state anger, blood pressure, and heart rate were assessed. Multivariate ANOVAs (four time of day conditions x three trials) revealed significant main effects for the trial factor for state anxiety, state anger, heart rate, and systolic blood pressure. State anxiety, state anger, and systolic blood pressure were found to be reduced at both the 10 and 20 min post-exercise assessment periods when compared with pre-exercise levels. ANOVAs performed on the difference scores showed that the mood improvements and cardiovascular changes were independent of the time of day that exercise was performed, and these findings were confirmed by ANCOVAs, which adjusted for differences in initial values across the four time of day conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Vertical transmission of human immunodeficiency virus from seronegative or indeterminate mothers.

UNLABELLED: OBJECTIVE--To describe the identification of human immunodeficiency virus (HIV)-infected infants born to women who were seronegative or indeterminate during pregnancy. RESEARCH DESIGN--Longitudinal cohort study. SETTING--Inner-city medical center. PARTICIPANTS: A series of children born to women with histories of risk factors for HIV infection were followed up for studies of the natural history of HIV-infected infants. These children were identified through risk factor assessment of pregnant women presenting for obstetric care. INTERVENTIONS--Counseling and testing to detect HIV. RESULTS--Three women were retrospectively identified who were infected with HIV during pregnancy but whose test results showed them to be either seronegative or indeterminate. Two of these women transmitted HIV infection to their children. Subsequently, all three women were confirmed to be infected. CONCLUSIONS--Standard serologic testing to detect HIV infection will not identify all infected pregnant women. Perinatal transmission of HIV can occur in women with negative results of enzyme-linked immunosorbent assay or indeterminate results of Western blot analysis during pregnancy.

AIDS Serodiagnosis↗
PubMed1990

Accelerator mass spectrometry in biomedical dosimetry: relationship between low-level exposure and covalent binding of heterocyclic amine carcinogens to DNA.

Accelerator mass spectrometry (AMS) is used to determine the amount of carcinogen covalently bound to mouse liver DNA (DNA adduct) following very low-level exposure to a 14C-labeled carcinogen. AMS is a highly sensitive method for counting long-lived but rare cosmogenic isotopes. While AMS is a tool of importance in the earth sciences, it has not been applied in biomedical research. The ability of AMS to assay rare isotope concentrations (10Be, 14C, 26Al, 41Ca, and 129I) in microgram amounts suggests that extension to the biomedical sciences is a natural and potentially powerful application of the technology. In this study, the relationship between exposure to low levels of 2-amino-3,8-dimethyl[2-14C]imidazo[4,5-f]quinoxaline and formation of DNA adducts is examined to establish the dynamic range of the technique and the potential sensitivity for biological measurements, as well as to evaluate the relationship between DNA adducts and low-dose carcinogen exposure. Instrument reproducibility in this study is 2%; sensitivity is 1 adduct per 10(11) nucleotides. Formation of adducts is linearly dependent on dose down to an exposure of 500 ng per kg of body weight. With the present measurements, we demonstrate at least 1 order of magnitude improvement over the best adduct detection sensitivity reported to date and 3-5 orders of magnitude improvement over other methods used for adduct measurement. An additional improvement of 2 orders of magnitude in sensitivity is suggested by preliminary experiments to develop bacterial hosts depleted in radiocarbon. Expanded applications involving human subjects, including clinical applications, are now expected because of the great detection sensitivity and small sample size requirements of AMS.

Animals↗
PubMed1990

Identical twins discordant for Kallmann's syndrome.

A 20 year old male patient presented with lack of sexual development. On examination he was eunuchoidal and hypogonadal, and olfactory function testing showed he was anosmic. Biochemical investigations proved he was hypogonadotrophic. Kallmann's syndrome was therefore diagnosed. His appearance was very different from his alleged identical twin who had undergone a normal puberty and had normal plasma testosterone and gonadotrophin levels. However, the twin was hyposmic. Genetic fingerprinting confirmed the twins were identical. Why Kallman's syndrome was incompletely expressed in one of them is unexplained. The parents and a normally menstruating sister had normal olfactory function.

Adult↗
PubMed1989

Healing of severe perineal and cutaneous Crohn's disease with hyperbaric oxygen.

Recurrent perineal Crohn's disease can be an extremely debilitating complication that may be difficult to treat. We report a patient with progressively worsening perineal and biopsy-proven cutaneous Crohn's disease that had been refractory to surgery and medical treatment (sulfasalazine, steroids, 6-mercaptopurine, metronidazole, antibiotics). As the lesions were reminiscent of problem wounds occurring in other situations, hyperbaric oxygen treatment was instituted while the patient was continued on metronidazole. Response was dramatic with almost immediate relief of symptoms and regression within 2.5 mo of wounds that had previously defied therapy for 8 yr. Clinical remission has not been sustained as four subsequent courses of hyperbaric oxygen have been given over a period of 11 mo. However, the patient has been essentially asymptomatic since her initial course and the extent of her cutaneous disease has been minimal compared with that before hyperbaric oxygen. Hyperbaric oxygen treatment is costly and should not be routinely used in every patient with perineal Crohn's disease. However, this case report may herald an advance in the understanding of the pathogenesis of this complication and ultimately, its therapy.

Combined Modality Therapy↗
PubMed1988

Failure of the sterile air-flow component of a protected environment detected by demonstration of Chaetomium species colonization of four consecutive immunosuppressed occupants.

Four bone marrow transplant recipients consecutively occupying the same room on our Oncology-Hematology Special Care Unit (OHSCU) became colonized with Chaetomium species between January and April, 1987. These patients, aged 27 to 43 years, were immunocompromised as a result of intensive chemotherapy, and were consequently at increased risk for development of invasive fungal infection. At the time of Chaetomium colonization, all patients were febrile, two had transient new infiltrates on chest x-ray, and three were receiving amphotericin B therapy. Subsequent environmental cultures revealed Chaetomium contamination of the OHSCU air-handling system, including the HEPA (high-efficiency particulate air) filters in seven of the nine rooms comprising the unit. Because fungal colonization of HEPA filters used to create a "protective environment" for immunocompromised patients can occur and can serve as a source for patient infections, guidelines concerning proper surveillance of these HEPA filters should be established. We suggest that before a new patient enters a "protected" room, the clean side of the HEPA filter should be cultured. If fungi are recovered from that culture, we would recommend changing the filter.

Adult↗